Scientists have inched a step closer to developing a first-of-its-kind drug to treat a chronic swelling condition that affects 10 million Americans.
Lymphedema is a chronic condition where fluids build up in the body, typically the arms or legs, causing swelling and skin damage that can make it difficult to move and complete everyday tasks.
There is no cure for the condition or medications specifically approved to treat it, leaving patients dependent on massage, compression garments, exercise and, in extreme cases, invasive surgery.
Now, researchers at Stanford University are working to develop a new medication to treat the condition.
In their new study, researchers recruited 23 patients suffering from lymphedema in their legs and gave them acebilustat, a newly-developed anti-inflammatory drug.
After patients took the drug once a day for a year, researchers found they had a five percent decrease in their leg volume, significantly improving their swelling.
Patients also saw reductions in skin thickness and scarring, which can happen due to swelling, as well as improvements to their quality of life.
The Stanford scientists said that while the drug is still undergoing clinical trials, they hope it can eventually work in tandem with conservative measures such as physical therapy, or as a standalone treatment, to reduce swelling in patients.
About 10 million Americans suffer from lymphedema, though there are limited treatments. An experimental drug may target a key inflammatory pathway
Dr Stanley Rockson, lead study author and Allan and Tina Neill Professor of Lymphatic Research and Medicine at Stanford University School of Medicine, said: ‘We hope that, ultimately, effective pharmacologic therapy could supplant physical self-care.
‘There could even be a role for disease prevention in high-risk patients.’
The drug works by reducing inflammation levels, which can help to reduce swelling.
When blood flows through capillaries, tiny blood vessels, small amounts of fluid leak out and into the surrounding tissue. Typically, this fluid is collected and drained away by the lymph system, a network of vessels and organs running throughout the body that are used to remove this liquid.
But in lymphedema, this drainage system does not work properly, leading to fluid accumulating and causing persistent swelling for sufferers.
In most cases, the condition develops after the lymphatic system has been damaged by cancer treatment, infection or injury. This is known as secondary lymphedema.
In some cases, however, patients suffer the condition due to the lymphatic system not developing properly. Experts believe this is usually genetic.
Without effective management, swelling can worsen over time. The buildup of fluid can also cause the skin and underlying tissues to harden and leave patients more vulnerable to potentially serious skin infections.
Current treatment methods, such as physical therapy, massage and compression garments, may only reduce swelling by up to 50 percent and are labor-intensive.
Rockson said: ‘It’s very labor-intensive; there’s a tremendous impact on quality of life to undertake this self-management and it’s expensive.’
In their new study, a phase 1 trial of the drug published in the journal Scientific Reports, scientists enrolled adults with stage two lymphedema in their legs. This is an advanced stage where swelling cannot be reversed with simple methods such as elevating the limbs.
Participants were 46 years old on average, with a body mass index of 26, classified as slightly overweight. About 57 percent were women and 57 percent had lymphedema in one limb rather than two.
About two-thirds were diagnosed with primary lymphedema.
Participants each took a 100mg acebilustat pill once per day for one year and continued existing self-management treatments such as massage and physical therapy.
Matthew Holbreich, pictured above, was diagnosed with lymphedema 23 years ago when he was a senior in college. He has seen significant improvements since starting the experimental drug acebilustat
Researchers measured their limb volume, skin thickness, tissue structure and quality of life at the start of the study and every three months after.
After 12 months, limb volume on average decreased by one liter, representing a 4.7 percent improvement.
Researchers also performed ultrasound scans in 20 of the participants, finding that 17 of them had changes to their tissue density and structure, suggesting the drug could treat years-long damage from lymphedema.
Additionally, participants reported improvements in their quality of life, including limb heaviness, tissue softness, how well their clothes fit, self-care, self-confidence and overall enjoyment of life.
There were no major side effects.
Two participants had elevated liver enzymes, which can signal potential liver damage, though these levels improved after stopping the medication. Two separate individuals experienced one instance each of cellulitis, a bacterial skin infection. They were both successfully treated with antibiotics.
Dr Stanley Rockson, pictured above, is working on clinical trials of acebilustat that will move the drug toward FDA approval
One of the participants who saw improvements was Matthew Holbreich, a software engineer who was diagnosed with lymphedema in his left leg 23 years ago, when he was a senior in college.
After his diagnosis, Holbreich was forced to give up contact sports and has suffered two infections that hospitalized him. After a year on acebilustat, his leg volume and skin smoothness have significantly improved.
‘The prospect of having a medication for lymphedema would be life-changing,’ Holbreich said.
‘I’ve been living with lymphedema for more than 20 years. It would be the most significant breakthrough for lymphedema treatment in my lifetime.’
The researchers believe acebilustat halts the production of leukotriene B4, or LTB4, a molecule found in higher levels in lymphedema patients that drives inflammation.
Rockson’s team has now launched a phase 2 trial of acebilustat comparing the drug to a placebo in patients with lymphedema in their arms. Those results are still pending, but he hopes that if the drug continues to show promise, the team can launch an additional trial seeking approval from the Food and Drug Administration.
‘We hope that, ultimately, effective pharmacologic therapy could supplant physical self-care. There could even be a role for disease prevention in high-risk patients,’ Rockson said.
‘We hope that, if we can carry this work forward, it’s going to make a major impact.’
